Journal of Natural Products 最新文献_第3页

Allantofuranone Biosynthesis and Precursor-Directed Mutasynthesis of Hydroxylated Analogues. 尿囊呋喃酮生物合成及羟基化类似物前体定向突变合成。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-05-23 Epub Date: 2025-04-18 DOI: 10.1021/acs.jnatprod.5c00197

Carsten Wieder, Claudia Simon-Sánchez, Johannes C Liermann, Rainer Wiechert, Karsten Andresen, Eckhard Thines, Till Opatz, Anja Schüffler

{"title":"Allantofuranone Biosynthesis and Precursor-Directed Mutasynthesis of Hydroxylated Analogues.","authors":"Carsten Wieder, Claudia Simon-Sánchez, Johannes C Liermann, Rainer Wiechert, Karsten Andresen, Eckhard Thines, Till Opatz, Anja Schüffler","doi":"10.1021/acs.jnatprod.5c00197","DOIUrl":"10.1021/acs.jnatprod.5c00197","url":null,"abstract":"Genome mining and heterologous reconstitution of biosynthetic genes in Aspergillus oryzae enabled elucidation of the hitherto elusive biosynthetic route that produces allantofuranone (1), a bioactive natural product originally isolated from Allantophomopsis lycopodina. The core non-ribosomal peptide synthetase (NRPS)-like enzyme AlfA of the alf BGC produces polyporic acid (2) from phenylpyruvic acid. In subsequent reactions, compound 2 is reductively dehydrated by the bifunctional enzyme AlfC and methylated by AlfD to produce terferol (6). In a final step, the quinol moiety of compound 6 is oxidatively cleaved and contracted by the aromatic ring cleavage dioxygenase AlfB. Using combinatorial biosynthesis, we were able to manipulate the biosynthetic route to yield hydroxylated pathway congeners, most notably the new natural products deoxyascocorynin (10), hydroxyterferol (11), and hydroxyallantofuranone (12).","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"1191-1200"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Furanoheliangolides from Centratherum punctatum and a General Approach for Stereochemical Assignment of Flexible Chiral Side Chains. 马尾草中呋喃heliangolides及柔性手性侧链立体化学配位的一般方法。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-05-22 DOI: 10.1021/acs.jnatprod.5c00329

Quan T Khong, Lindsay Marron, Shar-Yin Naomi Huang, Masoumeh Dalilian, Sourav Saha, Ekaterina I Goncharova, Girma M Woldemichael, Yves Pommier, Barry R O'Keefe, Brice A P Wilson, Lin Du

{"title":"Furanoheliangolides from Centratherum punctatum and a General Approach for Stereochemical Assignment of Flexible Chiral Side Chains.","authors":"Quan T Khong, Lindsay Marron, Shar-Yin Naomi Huang, Masoumeh Dalilian, Sourav Saha, Ekaterina I Goncharova, Girma M Woldemichael, Yves Pommier, Barry R O'Keefe, Brice A P Wilson, Lin Du","doi":"10.1021/acs.jnatprod.5c00329","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00329","url":null,"abstract":"Human topoisomerase 3β (TOP3B) is a potential molecular therapeutic target for cancer and viral infections. A high-throughput differential cell viability assay using colon cancer cell lines was developed to identify natural product modulators of TOP3B-associated cancer cell viability. The assay identified an organic extract of the plant Centratherum punctatum as having cytotoxic activity. Seven new furanoheliangolides, centratherolides A-G (1-7), along with two known analogues (2,3-epoxybutyryloxy)-goyazensolanolide (8) and goyazensolide (9), were isolated. Compounds 1, 8, and 9 exhibited selective cytotoxic activities against the TOP3B-knockout (TOP3B-KO) human colon carcinoma HCT116 cells compared with the wild-type HCT116 cells (TOP3B-WT). The challenging absolute configuration determination of the flexible chiral side chains in selected analogues (1-4 and 8) was resolved by combined approaches, including synthesis of chemical standards, DFT ECD calculation, and chiral HPLC analysis. Application of this elucidation methodology to a commercial sesquiterpene lactone clarified a contradiction in the stereochemical assignments reported for centaurepensin/chlorohyssopifolin A and 17-epi-chlorohyssopifolin A.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bipoladisins A-G, Uncommon Sesterterpenoids with Three Types of Carbon Skeletons from Bipolaris maydis and Their Reversal Activity on Paclitaxel Resistance. 双极甾烷类化合物A-G及其对紫杉醇抗性的逆转作用。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-05-21 DOI: 10.1021/acs.jnatprod.5c00024

Yong Shen, Qin Li, Nanjin Ding, Mengru Yu, Xiaoxia Gu, Weiguang Sun, Ying Tang, Chunmei Chen, Yonghui Zhang, Hucheng Zhu

引用次数: 0

Total Synthesis, Configuration, and Antiplasmodium Activity of Fusarihexin D and E and Analogues. Fusarihexin D和E及其类似物的合成、结构和抗疟原虫活性。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-05-21 DOI: 10.1021/acs.jnatprod.5c00282

Megan En Lee, Seetharamsing Balamkundu, Jiayong Liu, Donald Tay, Derek K Y Sim, Peter R Preiser, Chuan-Fa Liu

{"title":"Total Synthesis, Configuration, and Antiplasmodium Activity of Fusarihexin D and E and Analogues.","authors":"Megan En Lee, Seetharamsing Balamkundu, Jiayong Liu, Donald Tay, Derek K Y Sim, Peter R Preiser, Chuan-Fa Liu","doi":"10.1021/acs.jnatprod.5c00282","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00282","url":null,"abstract":"Fusarihexins C-E, a group of cyclodepsipeptides that contain a characteristic 2-hydroxy-4-methyl-pentanoic acid (HICA) residue, were recently isolated from the endophytic fungus Fusarium sp. The absolute stereochemistry of HICA was determined to be R in fusarihexin C using a modified Mosher's method. It was assumed that HICA in fusarihexins D and E would have the same configuration, as they are derived from the same biological source. Herein, we report the first total synthesis of the proposed structures of fusarihexins D and E as well as three new analogues. The compounds were synthesized by employing solid phase peptide synthesis (SPPS) and high dilution macrolactamization and characterized by NMR spectroscopy and high-resolution mass spectrometry (HRMS). Comparing the 1H and 13C NMR spectra of synthesized and natural compounds revealed that the HICA residue has the S-configuration in fusarihexin D. The antiplasmodium activity on Plasmodium falciparum and antitumor activity against MCF7 and A431 cells were also investigated. Encouragingly, fusarihexin D (with S-HICA) displayed potent antiplasmodium activity by interfering with the ring stage of the Plasmodium falciparum parasite life cycle (IC50 at 650 nM).","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Syntheses of Anti-Phytopathogenic Fungal 2,7'-Cyclo-7,8'-neolignan-Type Indanes and Preparation of 8'-Epimer. 抗植物病原真菌2,7′-环-7,8′-新木质素型吲哚烷的合成及8′-Epimer的制备。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-05-21 DOI: 10.1021/acs.jnatprod.5c00356

Ren Higuchi, Nao Kikuchi, Hisashi Nishiwaki, Koichi Akiyama, Satoshi Yamauchi

{"title":"Syntheses of Anti-Phytopathogenic Fungal 2,7'-Cyclo-7,8'-neolignan-Type Indanes and Preparation of 8'-Epimer.","authors":"Ren Higuchi, Nao Kikuchi, Hisashi Nishiwaki, Koichi Akiyama, Satoshi Yamauchi","doi":"10.1021/acs.jnatprod.5c00356","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00356","url":null,"abstract":"The anti-phytopathogenic fungal activities against Alternaria alternata (Japanese pear) pathotypes of (-)- and (+)-γ-diisoeugenol, which have (7S,7'S,8'S)- and (7R,7'R,8'R)-2,7'-cyclo-7,8'-neolignan-type indanes, respectively, are compared herein with the stereoisomers of 7,8'-epoxy-8,7'-neolignan, which have tetrahydrofuran structures. The results highlight the advantages of (7S,7'S,8'S)-2,7'-cyclo-7,8'-neolignan, (-)-γ-diisoeugenol. A series of derivatives with effective absolute configurations were synthesized with high stereoselectivity via intramolecular Friedel-Crafts reactions, and biological assays were performed. The most effective compound identified in this research was the (4-OCH3, 5-OCH3, 3'-CF3, 4'-OH)-derivative (EC50 = 8.6 μM). The combination of a hydrophobic group at the 3'-position and a phenolic hydroxy group at the 4'-position was crucial for the high activity. The 8'-epimer of the effective (7S,7'S,8'S)-2,7'-cyclo-7,8'-neolignan compound was also prepared by stereoselective hydrogenation of the 7-8' internal alkene. Thus, a novel anti-phytopathogenic fungal 2,7'-cyclo-7,8'-neolignan-type indane was developed.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Decoding Lusichelins A-E: An In-Depth Look at the Metallophores of Lusitaniella coriacea LEGE 07167-Structure, Production, and Functionality. 解码lusithelins A-E: coracea Lusitaniella lege07167的金属分子结构，生产和功能的深入研究。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-05-21 DOI: 10.1021/acs.jnatprod.5c00204

Maria Lígia Sousa, Leonor Ferreira, Dora Ferreira, Abel M Forero, Raquel Castelo-Branco, Nikoletta Szemerédi, Gabriella Spengler, Jaime Rodríguez, Carlos Jiménez, Pedro N Leão, Vitor Vasconcelos, Mariana Alves Reis

{"title":"Decoding Lusichelins A-E: An In-Depth Look at the Metallophores of Lusitaniella coriacea LEGE 07167-Structure, Production, and Functionality.","authors":"Maria Lígia Sousa, Leonor Ferreira, Dora Ferreira, Abel M Forero, Raquel Castelo-Branco, Nikoletta Szemerédi, Gabriella Spengler, Jaime Rodríguez, Carlos Jiménez, Pedro N Leão, Vitor Vasconcelos, Mariana Alves Reis","doi":"10.1021/acs.jnatprod.5c00204","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00204","url":null,"abstract":"Essential trace metals are vital for cellular processes, such as respiration, DNA replication, and photosynthesis. Cyanobacteria must tightly regulate metal homeostasis to prevent deficiency or toxicity, yet their metallophores remain overlooked. Here, we report lusichelins A-E (1-5), new metallophores isolated from the marine cyanobacterium Lusitaniella coriacea LEGE 07167. Their structures and configurational assignments were determined by using NMR, mass spectrometry, TD-DFT calculations, and retrobiosynthetic insights. Lusichelins feature a unique structural arrangement with thiazoline/thiazole rings connected via a vinyl group, an aliphatic carbon chain, or directly enabling the potential for metal coordination. Genomic analysis identified a hybrid PKS/NRPS biosynthetic gene cluster consistent with the lusichelin structure, bearing traits characteristic of metallophore biosynthesis. Functionally, lusichelins act as metallophores capable of chelating both iron and copper. Lusichelin C (3) consistently bound iron under both metal-rich and metal-limited culture conditions, while copper complexation was only observed under elevated copper levels. At physiologically relevant pH values, no significant metal-binding preference was detected. Moreover, compound production was maximized under metal-rich conditions and in response to copper limitation. Lusichelin B (2) exhibited cytotoxicity against colon carcinoma cells while reversing multidrug resistance via ABCB1 efflux pump modulation. These findings expand our understanding of cyanobacterial metallophores in microbial metal homeostasis and highlight their biological potential.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hypocrellin B Exerts Its Antitumor Effect on Colorectal Cancer by Inhibiting the AKT Pathway. Hypocrellin B通过抑制AKT通路对结直肠癌发挥抗肿瘤作用。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-05-20 DOI: 10.1021/acs.jnatprod.4c01431

Hongyan Qu, Aofeng Sun, Yi Zhou, Chunbo Ma, Yihan Ye, Yini Xu, Haiyang Zhao, Chengguang Zhao, Yunming Hu, Lehe Yang, Lingcong Peng, Suqing Zheng, Ke Wang

引用次数: 0

Discovery and Characterization of Actinosynnelassin: An Anti-Pseudomonas fluorescens Lasso Peptide Derived from a Large Precursor Open Reading Frame. 从大型前体开放阅读框中提取的抗荧光假单胞菌拉索肽——放线素synnelassin的发现和特性。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-05-19 DOI: 10.1021/acs.jnatprod.5c00312

Yu Wen, Zhiyu Li, Jiacai Ye, Xiaozheng Wang, Ming Jiang, Zixin Deng, Chunyang Cao, Xinyi He

{"title":"Discovery and Characterization of Actinosynnelassin: An Anti-Pseudomonas fluorescens Lasso Peptide Derived from a Large Precursor Open Reading Frame.","authors":"Yu Wen, Zhiyu Li, Jiacai Ye, Xiaozheng Wang, Ming Jiang, Zixin Deng, Chunyang Cao, Xinyi He","doi":"10.1021/acs.jnatprod.5c00312","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00312","url":null,"abstract":"Lasso peptides, a unique class of ribosomally synthesized and post-translationally modified peptide (RiPP), are challenging to synthesize chemically, making the discovery of new peptides and their biosynthetic pathways essential. This study reports the discovery and characterization of a novel lasso peptide, actinosynnelassin, from Actinosynnema pretiosum subsp. auranticum DSM 44131. By overexpressing an endogenous TetR/AcrR family regulator and employing OSMAC (One Strain Many Compounds)-guided fermentation screening, several endogenous secondary metabolite biosynthetic gene clusters (BGCs) were activated, resulting in the isolation of actinosynnelassin. The 3D structure of actinosynnelassin, confirmed by nuclear magnetic resonance (NMR) NOE-derived distance constraints, features a 9-aa macrolactam ring, a 6-aa loop, and a 2-aa tail, with the ring encircling the tail between three aromatic bulkier residues. The minimal inhibitory concentration (MIC) tests indicate that actinosynnelassin inhibits several Gram-positive bacteria and Pseudomonas fluorescens, making it the first reported lasso peptide to inhibit P. fluorescens. The predicted open reading frame (ORF) of the precursor peptide may be translated into a 331-aa fusion protein featuring an N-terminal AraC/XylS family transcriptional regulator, making it longer than typical lasso precursors. Thus, discovering this large precursor ORF enhances our understanding of lasso peptide BGCs with unusual architectures and enables the finding of other unique lasso peptides.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Total Synthesis and SARS-CoV-2 3CLpro Inhibition Activities of (±)-Tuaimenal A and Its Derivatives. （±）-Tuaimenal A及其衍生物的总合成及其对sars - cov - 23clpro的抑制活性

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-05-19 DOI: 10.1021/acs.jnatprod.5c00251

Zeyu Tao, Jichen Guan, Guangyan Zhang, Junyi Liu, Xuan Pan, Fangfang Lai, Zhanzhu Liu

引用次数: 0

Ouhanamide, an Antiparasitic Linear Lipopeptide from a Marine Okeania sp. Cyanobacterium. 海洋蓝藻属的抗寄生线状脂肽Ouhanamide。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-05-16 DOI: 10.1021/acs.jnatprod.5c00281

Mizuho Niiyama, Naoaki Kurisawa, Kairi Umeda, Ghulam Jeelani, Adnan Luthfi Agusta, Tomoyoshi Nozaki, Kiyotake Suenaga

引用次数: 0